Fetal membranes and microbial threats

Bacterial chorioamnionitis — infection of the membranes surrounding the developing fetus — is a major cause of preterm birth and other adverse pregnancy outcomes.

The outermost layer of the gestational membrane, the decidua, is a potential entry point for bacteria. David Aronoff, MD, and colleagues explored how communication between decidual stromal cells and immune cells (macrophages) may shape the response to microbes.

In co-cultures of the two cell types, they found that the bacterial component LPS enhanced production of most inflammatory mediators, but that macrophage-generated TNF-alpha was suppressed.

TNF-alpha is a highly inflammatory molecule, and turning its production off (or down) might be beneficial, by limiting inflammation-induced tissue damage. It might instead cause hard, by impairing immune defenses against infection, possibly helping bacteria instead of the pregnant mother. Regardless, this suppression appeared to be mediated by decidual cell production of a small molecule called prostaglandin E2 (PGE2).

A technological innovation of this research is that Aronoff and his team collaborated with biomedical engineers to create a simplified gestational membrane-on-a-chip device to more closely model events happening in the pregnant uterus.

Also, in a mouse model of bacterial chorioamnionitis caused by Group B Streptococcus, macrophages accumulated at sites of bacterial invasion, and PGE2 levels in amniotic fluid were increased, suggesting that what was observed in the laboratory might be happening in an infected patient.

The findings, reported in the American Journal of Reproductive Immunology, suggest that decidual stromal cells release PGE2 to modulate tissue responses to microbial threats. Defining early signaling events in chorioamnionitis may reveal targets for disease prevention or therapy.

This research was supported by grants from the Global Alliance to Prevent Prematurity and Stillbirth, the March of Dimes, the National Institutes of Health (HD068256, AI007474, HD060554) and by the U.S. Environmental Protection Agency.